It is urgent to find a technology accurately to better diagnose and treat to brain tumor.Eu-doped Gd2 O3 nanorods(Eu-Gd2 O3 NRs)with paramagnetic and fluorescent properties were conjugated with doxorubicin(Dox)and chl...It is urgent to find a technology accurately to better diagnose and treat to brain tumor.Eu-doped Gd2 O3 nanorods(Eu-Gd2 O3 NRs)with paramagnetic and fluorescent properties were conjugated with doxorubicin(Dox)and chlorotoxin(CTX)via PEGylation,hydrazone bond and sulfur bond(named as CTXNRs-Dox),and these NRs could release more Dox in lower pH environment.The results of cell experiments indicated that CTX-NRs-Dox had obvious targeting and toxic effects on U251 cells,as well as good fluorescence imaging behavior.The orthotopic glioma-transplanted mice models were constructed via the intracranial injection of glioma cells(U87 MG).The result of experiments after the tail-vein injection of the prepared NRs suggested that CTX-NRs-Dox could target to brain tumors via the long-time blood circulation,leading to their obvious contrast enhancement of MR imaging of the intracranial tumor and their significant inhibitory effect on the growth and metastasis of brain tumors.A mechanism of synergistic effect of CTX-NRs-Dox on targeting and inhabiting the brain tumor was proposed.Our research suggested that CTX-NRs-Dox had potential application prospect in the detection and treatment of glioma.展开更多
Apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) can be regulated by the epidermal growth factor(EGF) signaling pathway.In this study,recombinant adenoviral vectors that encode TRAIL...Apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) can be regulated by the epidermal growth factor(EGF) signaling pathway.In this study,recombinant adenoviral vectors that encode TRAIL gene from the hTERT/RGD promoter(AdTRAIL) was combined with drugs including gefitinib,elotinib,and cetuximab that inhibit EGFR and the EGF signaling pathway in non-small cell lung cancer(NSCLC) cell lines to investigate their antitumor activity.In vitro,compared to single reagent,AdTRAIL combined with EGFR inhibitors reduced proliferation and enhanced apoptosis in H460,A549,and SW1573 cell lines.Western blot results suggested that these effects were relative to up-regulation of pro-apoptosis protein BAX and down-regulation of p-AKT.In vivo,AdTRAIL combined with cetuximab resulted in a significant growth reduction in H460 xenografts without damage to the main organs of nude mice.Histological examination and TUNEL analyses of xenografts showed that cetuximab enhanced cell apoptosis induced by AdTRAIL.These results indicate that EGFR inhibitors enhanced AdTRAIL anti-tumor activity in NSCLC cell lines and that inhibiting the AKT pathway played an important role in this enhancement.展开更多
The components of the tumor microenvironment(TME)in solid tumors,especially chemokines,are currently attracting much attention from scientists.C-X-C motif chemokine ligand 5(CXCL5)is one of the important chemokines in...The components of the tumor microenvironment(TME)in solid tumors,especially chemokines,are currently attracting much attention from scientists.C-X-C motif chemokine ligand 5(CXCL5)is one of the important chemokines in TME.Over-expression of CXCL5 is closely related to the survival time,recurrence and metasta-sis of cancer patients.In TME,CXCL5 binds to its receptors,such as C-X-C motif chemokine receptor 2(CXCR2),to participate in the recruitment of immune cells and promote angiogenesis,tumor growth,and metastasis.The CXCL5/CXCR2 axis can act as a bridge between tumor cells and host cells in TME.Blocking the trans-mission of CXCL5/CXCR2 signals can increase the sensitivity and effectiveness of immunotherapy and slow down tumor progression.CXCL5 and CXCR2 are also regarded as biomarkers for predicting prognosis and molecular targets for customiz-ing the treatment.In this review,we summarized the current literature regarding the biological functions and clinical significance of CXCL5/CXCR2 axis in TME.The possibility to use CXCL5 and CXCR2 as potential prognostic biomarkers and thera-peutic targets in cancer is also discussed.展开更多
高迁移率族蛋白N2(high mobility group N2,HMGN2)是高迁移率族蛋白N(high mobility group N,HMGN)家族成员,是一种广泛存在于真核生物染色质内的非组蛋白。研究发现,HMGN2可抑制人口腔鳞状细胞癌、子宫肌瘤、肺癌、骨肉瘤等肿瘤细胞的...高迁移率族蛋白N2(high mobility group N2,HMGN2)是高迁移率族蛋白N(high mobility group N,HMGN)家族成员,是一种广泛存在于真核生物染色质内的非组蛋白。研究发现,HMGN2可抑制人口腔鳞状细胞癌、子宫肌瘤、肺癌、骨肉瘤等肿瘤细胞的增殖,而在慢性白血病肿瘤细胞中,HMGN2却异常高表达,说明HMGN2在不同肿瘤中可能发挥着不同的作用。本文总结了HMGN2在不同肿瘤中的表达情况与意义,并探讨了其在肿瘤治疗中的潜在作用。展开更多
背景与目的:靶向治疗是乳腺癌等实体瘤治疗的又一有效手段,靶向药物的开发是临床治疗的需要。本文探讨哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)特异性抑制剂雷帕霉素和甲基转移酶抑制剂5-脱氧氮杂胞苷(5-aza-2’-de...背景与目的:靶向治疗是乳腺癌等实体瘤治疗的又一有效手段,靶向药物的开发是临床治疗的需要。本文探讨哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)特异性抑制剂雷帕霉素和甲基转移酶抑制剂5-脱氧氮杂胞苷(5-aza-2’-deoxycytidine,5-Aza-cdR)对雌激素受体阴性人乳腺癌细胞株MCF-7体外培养的抑制作用,为临床靶向治疗提供实验依据。方法:取对数生长期生长良好的乳腺癌MCF-7细胞株,按2.0×106细胞/孔接种于24孔板,按析因试验设置4个组:雷帕霉素组(R组)、5-Aza-cdR组(Aza组)、两药联合组和对照组。采用MTT法观察雷帕霉素、5-Aza-cdR对体外培养的MCF-7细胞系生长的抑制作用;应用流式细胞仪检测凋亡细胞和细胞周期。结果:与对照组相比,R组和Aza组均有一定的抑制乳腺癌细胞MCF-7细胞体外培养生长的作用(P<0.05),联合组对乳腺癌细胞生长的抑制作用与R组相同(P>0.05)。在干预48h时,R组和联合组即达到有效抑制率。Aza组干预120h达到有效抑制率。Aza组细胞抑制率低于联合组(P<0.05),R组与联合组细胞抑制率差异无显著性(P>0.05)。在72h时间点,R组、Aza组、联合组、对照组的早期凋亡细胞百分率分别为40.9%、22.7%、37.3%、24.1%;晚期凋亡细胞分别为17.8%、43.7%、27%、40.2%;与对照组相比,R组、联合组均能有效地诱导MCF-7早期细胞凋亡(P<0.05)。Aza组早期细胞凋亡率均较R组和联合组低(P<0.05),但晚期细胞凋亡率较R组和联合组高(P<0.05);与对照组相比差异无显著性(P>0.05)。雷帕霉素4.0×10-5mg/L与5-Aza-cdR25μmol/L干预无明显交互作用(P>0.05)。联用组与R组比较,细胞早期凋亡率下降(P<0.05)。在72h时间点,4组的G0、G1期细胞分别为60.1%、67.3%、66.8%和6%;S期细胞分别为34.2%、17.1%、22.2%和38.5%;G2期细胞分别为5.8%、15.6%、11.1%和55.4%。与对照组比较,R组、Aza组、联合组对乳腺癌MCF-7细胞均有较强的G0、G1期阻滞作用(P<0.05)。与联合组相比联合用药不增强G0、G1期周期阻滞作用(P>0.05)。雷帕霉素4.0×10-5mg/L与5-Aza-cdR25μmol/L干预在细胞G0、G1期无明显的交互作用(P>0.05)。结论:体外培养抑制试验证明,雷帕霉素、5-Aza-cdR均能抑制乳腺癌细胞株MCF-7的生长。两药无交互作用,临床无联合用药价值。雷帕霉素联合5-Aza-cdR不增加细胞凋亡。5-Aza-cdR能干预细胞周期,其可能的机制是诱导细胞成熟分化。联合用药不增强MCF-7细胞的周期阻滞和凋亡。展开更多
基金supported by the National Natural Science Foundation of China (Nos.51273122,51872190)Sichuan Science and Technology Project (No.2018JY0535)supported by the Fundamental of Research Funds for the Central University (Nos.SCU2017A001,2018SCUH0024)
文摘It is urgent to find a technology accurately to better diagnose and treat to brain tumor.Eu-doped Gd2 O3 nanorods(Eu-Gd2 O3 NRs)with paramagnetic and fluorescent properties were conjugated with doxorubicin(Dox)and chlorotoxin(CTX)via PEGylation,hydrazone bond and sulfur bond(named as CTXNRs-Dox),and these NRs could release more Dox in lower pH environment.The results of cell experiments indicated that CTX-NRs-Dox had obvious targeting and toxic effects on U251 cells,as well as good fluorescence imaging behavior.The orthotopic glioma-transplanted mice models were constructed via the intracranial injection of glioma cells(U87 MG).The result of experiments after the tail-vein injection of the prepared NRs suggested that CTX-NRs-Dox could target to brain tumors via the long-time blood circulation,leading to their obvious contrast enhancement of MR imaging of the intracranial tumor and their significant inhibitory effect on the growth and metastasis of brain tumors.A mechanism of synergistic effect of CTX-NRs-Dox on targeting and inhabiting the brain tumor was proposed.Our research suggested that CTX-NRs-Dox had potential application prospect in the detection and treatment of glioma.
文摘Apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) can be regulated by the epidermal growth factor(EGF) signaling pathway.In this study,recombinant adenoviral vectors that encode TRAIL gene from the hTERT/RGD promoter(AdTRAIL) was combined with drugs including gefitinib,elotinib,and cetuximab that inhibit EGFR and the EGF signaling pathway in non-small cell lung cancer(NSCLC) cell lines to investigate their antitumor activity.In vitro,compared to single reagent,AdTRAIL combined with EGFR inhibitors reduced proliferation and enhanced apoptosis in H460,A549,and SW1573 cell lines.Western blot results suggested that these effects were relative to up-regulation of pro-apoptosis protein BAX and down-regulation of p-AKT.In vivo,AdTRAIL combined with cetuximab resulted in a significant growth reduction in H460 xenografts without damage to the main organs of nude mice.Histological examination and TUNEL analyses of xenografts showed that cetuximab enhanced cell apoptosis induced by AdTRAIL.These results indicate that EGFR inhibitors enhanced AdTRAIL anti-tumor activity in NSCLC cell lines and that inhibiting the AKT pathway played an important role in this enhancement.
基金the Project of Jiangsu Provincial Key medical talents in Jiangsu Province,Grant/Award Number:ZDRCA2016034。
文摘The components of the tumor microenvironment(TME)in solid tumors,especially chemokines,are currently attracting much attention from scientists.C-X-C motif chemokine ligand 5(CXCL5)is one of the important chemokines in TME.Over-expression of CXCL5 is closely related to the survival time,recurrence and metasta-sis of cancer patients.In TME,CXCL5 binds to its receptors,such as C-X-C motif chemokine receptor 2(CXCR2),to participate in the recruitment of immune cells and promote angiogenesis,tumor growth,and metastasis.The CXCL5/CXCR2 axis can act as a bridge between tumor cells and host cells in TME.Blocking the trans-mission of CXCL5/CXCR2 signals can increase the sensitivity and effectiveness of immunotherapy and slow down tumor progression.CXCL5 and CXCR2 are also regarded as biomarkers for predicting prognosis and molecular targets for customiz-ing the treatment.In this review,we summarized the current literature regarding the biological functions and clinical significance of CXCL5/CXCR2 axis in TME.The possibility to use CXCL5 and CXCR2 as potential prognostic biomarkers and thera-peutic targets in cancer is also discussed.
文摘高迁移率族蛋白N2(high mobility group N2,HMGN2)是高迁移率族蛋白N(high mobility group N,HMGN)家族成员,是一种广泛存在于真核生物染色质内的非组蛋白。研究发现,HMGN2可抑制人口腔鳞状细胞癌、子宫肌瘤、肺癌、骨肉瘤等肿瘤细胞的增殖,而在慢性白血病肿瘤细胞中,HMGN2却异常高表达,说明HMGN2在不同肿瘤中可能发挥着不同的作用。本文总结了HMGN2在不同肿瘤中的表达情况与意义,并探讨了其在肿瘤治疗中的潜在作用。
文摘背景与目的:靶向治疗是乳腺癌等实体瘤治疗的又一有效手段,靶向药物的开发是临床治疗的需要。本文探讨哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)特异性抑制剂雷帕霉素和甲基转移酶抑制剂5-脱氧氮杂胞苷(5-aza-2’-deoxycytidine,5-Aza-cdR)对雌激素受体阴性人乳腺癌细胞株MCF-7体外培养的抑制作用,为临床靶向治疗提供实验依据。方法:取对数生长期生长良好的乳腺癌MCF-7细胞株,按2.0×106细胞/孔接种于24孔板,按析因试验设置4个组:雷帕霉素组(R组)、5-Aza-cdR组(Aza组)、两药联合组和对照组。采用MTT法观察雷帕霉素、5-Aza-cdR对体外培养的MCF-7细胞系生长的抑制作用;应用流式细胞仪检测凋亡细胞和细胞周期。结果:与对照组相比,R组和Aza组均有一定的抑制乳腺癌细胞MCF-7细胞体外培养生长的作用(P<0.05),联合组对乳腺癌细胞生长的抑制作用与R组相同(P>0.05)。在干预48h时,R组和联合组即达到有效抑制率。Aza组干预120h达到有效抑制率。Aza组细胞抑制率低于联合组(P<0.05),R组与联合组细胞抑制率差异无显著性(P>0.05)。在72h时间点,R组、Aza组、联合组、对照组的早期凋亡细胞百分率分别为40.9%、22.7%、37.3%、24.1%;晚期凋亡细胞分别为17.8%、43.7%、27%、40.2%;与对照组相比,R组、联合组均能有效地诱导MCF-7早期细胞凋亡(P<0.05)。Aza组早期细胞凋亡率均较R组和联合组低(P<0.05),但晚期细胞凋亡率较R组和联合组高(P<0.05);与对照组相比差异无显著性(P>0.05)。雷帕霉素4.0×10-5mg/L与5-Aza-cdR25μmol/L干预无明显交互作用(P>0.05)。联用组与R组比较,细胞早期凋亡率下降(P<0.05)。在72h时间点,4组的G0、G1期细胞分别为60.1%、67.3%、66.8%和6%;S期细胞分别为34.2%、17.1%、22.2%和38.5%;G2期细胞分别为5.8%、15.6%、11.1%和55.4%。与对照组比较,R组、Aza组、联合组对乳腺癌MCF-7细胞均有较强的G0、G1期阻滞作用(P<0.05)。与联合组相比联合用药不增强G0、G1期周期阻滞作用(P>0.05)。雷帕霉素4.0×10-5mg/L与5-Aza-cdR25μmol/L干预在细胞G0、G1期无明显的交互作用(P>0.05)。结论:体外培养抑制试验证明,雷帕霉素、5-Aza-cdR均能抑制乳腺癌细胞株MCF-7的生长。两药无交互作用,临床无联合用药价值。雷帕霉素联合5-Aza-cdR不增加细胞凋亡。5-Aza-cdR能干预细胞周期,其可能的机制是诱导细胞成熟分化。联合用药不增强MCF-7细胞的周期阻滞和凋亡。
